Managing factor Xa (FXa) inhibitor–treated patients with related life-threatening bleeds

What are the risks for major bleeding while on rivaroxaban or apixaban?

Various guidelines recommend treatment with FXa inhibitors, a type of anticoagulant such as rivaroxaban and apixaban, for patients with venous thromboembolism and atrial fibrillation to prevent clot formation.1-4 While these therapies do reduce the risk of blood clots and ischemic events, they also pose a risk to patients of increased bleeding as a result of their anticoagulant effects, which in some cases can become life-threatening.5

There are approximately 6 million people in the United States treated with FXa inhibitors, and there are over 198,000 hospitalizations from FXa inhibitor–associated major bleeding events annually.5,6 FXa inhibitors are blood-thinning medications, meaning they interfere with the body’s normal clotting process. This can contribute to an overall risk of bleeding, ranging from less severe to life-threatening. The reported risk of major bleeding in patients with nonvalvular atrial fibrillation is reported to be 3.6% for rivaroxaban and 1.41% to 2.13% for apixaban.7,8

FXa inhibitor–related major bleeds can present in various sites of the body, such as the brain, gastrointestinal tract, inside the abdominal cavity, lungs, and a variety of other places due to trauma.5 A bleeding event is considered life-threatening when there is a reduction in hemoglobin of at least 2 g/dL, when the bleed is associated with signs or symptoms of hemodynamic compromise, or when there is bleeding into a critical area or organ.9 These major bleeding events are associated with a significantly increased risk for death.5

About 410 patients each day were expected to be hospitalized with an apixaban- or rivaroxaban-related bleed in 2018.9 It is estimated that approximately 70 patients die each day following hospitalization for bleeding related to rivaroxaban or apixaban.6,10,11

Symptoms of FXa bleeds

  • Uncontrolled or life-threatening bleeds


  1. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149(2):315-352.
  2. Camm AJ, Lip GY, De Caterina R, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33(21):2719-2747.
  3. Writing Group Members, January CT, Wann LS, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm. 2019;16(8):e66-e93.
  4. Konstantinides SV, Torbicki A, Agnelli G, et al. 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014;35(43):3033-3069k.
  5. Tomaselli GF, Mahaffey KW, Cuker A, et al. 2017 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol. 2017;70(24):3042-3067.
  6. Data on file. Alexion Pharmaceuticals, Inc.
  7. Xarelto [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc; 2019.
  8. Eliquis [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2019.
  9. Connolly SJ, Crowther M, Eikelbloom JW, et al. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Engl J Med. 2019;380(14):1326-1335.
  10. Piccini JP, Garg J, Patel MR, et al. Management of major bleeding events in patients treated with rivaroxaban vs. warfarin: results from the ROCKET AF trial. Eur Heart J. 2014;35(28):1873-1880.
  11. Held C, Hylek EM, Alexander JH, et al. Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial. Eur Heart J. 2015;36(20):1264-1272.

Victor, diagnosed with PNH at 27 years old
Now I know that others can benefit from my experience and I want to be an inspiration to them.”